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两种单环β-内酰胺抗生素(氨曲南和诺卡菌素A)在水溶液中的稳定性

Stability in aqueous solution of two monocyclic beta-lactam antibiotics: aztreonam and nocardicin A.

作者信息

Méndez R, Alemany T, Martín-Villacorta J

机构信息

Departamento de Bioquímica y Biología Molecular, Facultades de Biología y Veterinaria, Universidada de León, Spain.

出版信息

Chem Pharm Bull (Tokyo). 1992 Dec;40(12):3222-7. doi: 10.1248/cpb.40.3222.

DOI:10.1248/cpb.40.3222
PMID:1294324
Abstract

The catalytic effect of various buffer systems (citrates, acetates, phosphates, borates and carbonates) on the degradation of aztreonam and nocardicin A in aqueous solution was studied at 35 degrees C and a constant ionic strength of 0.5 mol.dm-3 over a pH range of 3.50 to 10.50. The observed degradation rates, obtained by measuring the remaining intact antibiotic, were shown to follow pseudo-first-order kinetics with regard to antibiotic concentrations and to be influenced by general acid and general base catalysis. The changes in the concentration of intact beta-lactam antibiotic in the solutions were established by reverse-phase HPLC with UV-detection. In general the buffer systems employed in the kinetic studies showed a very weak catalytic effect on the degradation of aztreonam and nocardicin A. The pH-rate profiles for these antibiotics showed degradation minimums at pH 5.38 and 6.13, respectively. Aztreonam is slightly more reactive with hydrogen ions than nocardicin A and is much more reactive with hydroxide ions. In comparison with other beta-lactamic antibiotics, aztreonam and nocardicin A are much more stable in aqueous solution, except for aztreonam in a base solution, which is just as unstable as penicillins and cephalosporins. The Arrhenius activation energies were determined for aztreonam and nocardicin A at pH's 4.23, 6.59 and 8.60.

摘要

在35℃和0.5 mol·dm⁻³的恒定离子强度下,于pH值3.50至10.50范围内,研究了各种缓冲体系(柠檬酸盐、醋酸盐、磷酸盐、硼酸盐和碳酸盐)对水溶液中氨曲南和诺卡菌素A降解的催化作用。通过测量剩余完整抗生素获得的观测降解速率,显示出在抗生素浓度方面遵循准一级动力学,并受广义酸和广义碱催化的影响。溶液中完整β-内酰胺抗生素浓度的变化通过反相高效液相色谱-紫外检测来确定。一般而言,动力学研究中使用的缓冲体系对氨曲南和诺卡菌素A的降解显示出非常弱的催化作用。这些抗生素的pH-速率曲线分别在pH 5.38和6.13处显示出降解最小值。氨曲南与氢离子的反应性比诺卡菌素A略高,与氢氧根离子的反应性则高得多。与其他β-内酰胺抗生素相比,氨曲南和诺卡菌素A在水溶液中更稳定,除了氨曲南在碱性溶液中,其稳定性与青霉素和头孢菌素一样差。测定了氨曲南和诺卡菌素A在pH值4.23、6.59和8.60时的阿仑尼乌斯活化能。

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Stability in aqueous solution of two monocyclic beta-lactam antibiotics: aztreonam and nocardicin A.两种单环β-内酰胺抗生素(氨曲南和诺卡菌素A)在水溶液中的稳定性
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